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Ann Thorac Surg 2005;80:1979-1980
© 2005 The Society of Thoracic Surgeons
Division of Cardiothoracic Surgery, University of North Carolina at Chapel Hill, CB 7065, Medical School Wing C, Room 354, Chapel Hill, NC 27599-7065
(Email: fdetter{at}med.unc.edu).
The article by Birim and colleagues [1] is a sophisticated comparison of the reliability of chest computed tomography (CT) with positron emission tomography (PET) for mediastinal staging of nonsmall cell lung cancer (NSCLC). Using meta-analysis and summary receiver operating characteristic curves, the study convincingly demonstrates that mediastinal staging by CT is not adequate, and PET is significantly better. Thus PET represents progress in staging of the NSCLC.
In assessing progress, it is useful to reflect on the past. For example, in the 1980s it became clear that NSCLC and small cell lung cancer exhibited different behaviors and should be considered separately. Mediastinoscopy became an accepted technique of mediastinal staging among serious thoracic surgeons. The development of computed tomographic scanning allowed unprecedented preoperative anatomic definition. Many studies of mediastinal staging by CT were conducted involving thousands of patients, and it became clear that CT was not sufficiently reliable for many subgroups of patients. In particular, further investigation was needed in patients with enlarged discrete nodes (40% false positives) or with normal sized N2, N3 nodes in the face of a central tumor, N1 nodal enlargement, or an adenocarcinoma (20% to 25% false negatives) [2]. A chest computed tomographic scan followed by mediastinoscopy in most patients became the standard method of thorough mediastinal staging.
In the 1990s, PET became available, permitting an assessment of differences in cellular metabolism. Positron emission tomographic scanning was useful in suggesting the diagnosis in indeterminate pulmonary nodules, in detecting potential extrathoracic metastases, and in detecting mediastinal uptake suggestive of malignant involvement. At the same time, new methods of cytologic confirmation of mediastinal nodes became more available, such as transbronchial or ultrasound with transesophageal needle aspiration.
Now, in 2005, much literature exists evaluating the efficacy of PET for mediastinal staging, making a meta-analysis such as that by Birim and colleagues [1] possible. The literature involves many hundreds of patients (833 to be exact), but unfortunately definition of efficacy in subgroups is very limited because of poorly defined patient cohorts. Most studies have compared the reliability of CT to PET. These studies have taught us that mediastinal staging by CT is not very reliable, and that PET is clearly better.
Is this progress or are we re-learning old lessons? Why is PET compared with CT, as if CT was the standard? Have we forgotten that CT is notoriously inaccurate for many patients? Have we forgotten how to perform invasive staging of the mediastinum? Have we become polarized between experts who have all of the nuances and staging tools in their repertoire, and those who seek a unified noninvasive approach for all patients in order to avoid invasive staging or consideration of subgroups? Perhaps the focus on PET versus CT is because this literature has been written primarily by radiologists, who do not have access to clinical information or understand the role of other mediastinal staging tests. To really make progress, we must not forget but build on the past, yet be willing to discard old approaches when they have become obsolete.
When a new test becomes available, we must thoughtfully add it to the standard approach where it will either add something or substitute for another one. The article by Birim and colleagues [1] does not tell us whether or when PET can replace mediastinoscopy or other mediastinal biopsy techniques. There is a general consensus that mediastinal PET uptake requires biopsy confirmation (15% false positives) [3, 4]. A negative PET of the mediastinum is generally quite reliable (< 10% false negatives), but we do not know whether this is true for those patient subgroups with a high incidence of N2, N3 involvement despite a negative computed tomographic scan [4]. Furthermore, confirmation of the diagnosis (instead of confirmation of staging) may require mediastinal biopsy. Thus, invasive biopsy of the mediastinum is not obsolete.
The review by Birim and colleagues [1] falls into the same trap as much of the PET literature by ignoring the potential role of invasive staging tests. It is certainly better to get a positron emission tomographic scan than to rely on a computed tomographic scan alone if invasive tests or thoughtful consideration of patient subgroups are not available. A more appropriate approach is to define when PET should be used to help stage patients more accurately, based on the clinical and CT evaluation of the patient, rather than advocate PET for all.
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  O. Birim, A. P. Kappetein, and A. J.J.C. Bogers Reply Ann. Thorac. Surg., November 1, 2005; 80(5): 1980 - 1981. [Full Text] [PDF]
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